Changes in serum uric acid levels as a predictor of future decline in renal function in older adults with type 2 diabetes.

ABSTRACT: Given that factors affecting renal function remain unknown, this study aimed to identify key predictors of estimated glomerular filtration rate (eGFR) deterioration, which is a representative of renal function decline in older adults with type 2 diabetes (T2DM). In an exploratory prospective observational study, we enrolled 268 Japanese people with T2DM aged ≥20 years who were followed up at Shinshu University Hospital. Among those, 112 eligible individuals aged ≥65 years were included in the present study. Factors associated with 3-year changes in eGFR (ΔeGFR) and eGFR deterioration (ΔeGFR < 0) were identified using bivariate and multivariable analyses. Regarding baseline values of the subjects, the mean age was 73.5 years, mean blood pressure was 131/74 mm Hg, mean hemoglobin A1c was 7.1%, mean eGFR was 62.0 mL/min/1.73 m2, mean urinary albumin excretion was 222.6 mg/gCre, and mean serum uric acid (UA) was 5.5 mg/mL. In bivariate analysis, the 3-year change in UA (ΔUA) levels was significantly correlated with ΔeGFR (r = -0.491, P < .001), but the baseline UA was not (r = 0.073, P = .444). Multiple linear regression analysis revealed that ΔUA was a significant negative predictor of ΔeGFR in the model that included sex, age, body mass index, serum albumin, and ΔUA as explanatory variables. Moreover, multiple logistic regression analysis demonstrated that ΔUA had a positive association with ΔeGFR <0 (odds ratio 2.374; 95% confidence interval 1.294-4.357). Thus, future renal function decline can be predicted by ΔUA but not by baseline UA in older adults with T2DM. Further research is needed to determine whether lowering the serum UA level can prevent eGFR decline.

Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells.

The mechanism whereby 17ß-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10-9 to 1 × 10-7 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of the insulin promoter region revealed that nucleotide positions - 238 to - 144 (relative to the transcriptional start site) were needed for ER repression of the rat insulin II gene. PDX1- and BETA2-binding sites were required for the repression, but an estrogen response element-like sequence or an AP1 site in the promoter was not involved. In conclusion, we found that estrogen repressed insulin mRNA expression in a beta cell line. In addition, the ER suppressed insulin gene transcription in a ligand-independent matter. These observations suggest ER may regulate insulin transcription by indirect genomic signaling.

Loss of µ-crystallin causes PPARγ activation and obesity in high-fat diet-fed mice.

The thyroid hormone-binding protein µ-crystallin (CRYM) mediates thyroid hormone action by sequestering triiodothyronine in the cytoplasm and regulating the intracellular concentration of thyroid hormone. As thyroid hormone action is closely associated with glycolipid metabolism, it has been proposed that CRYM may contribute to this process by reserving or releasing triiodothyronine in the cytoplasm. We aimed to clarify the relationship between CRYM and glycolipid metabolism by comparing wild-type and CRYM knockout mice fed a high-fat diet. Each group was provided a high-fat diet for 10 weeks, and then their body weight and fasting blood glucose levels were measured. Although no difference in body weight was observed between the two groups with normal diet, the treatment with a high-fat diet was found to induce obesity in the knockout mice. The knockout group displayed increased dietary intake, white adipose tissue, fat cell hypertrophy, and hyperglycemia in the intraperitoneal glucose tolerance test. In CRYM knockout mice, liver fat deposits were more pronounced than in the control group. Enhanced levels of PPARγ, which is known to cause fatty liver, and ACC1, which is a target gene for thyroid hormone and is involved in the fat synthesis, were also detected in the livers of CRYM knockout mice. These observations suggest that CRYM deficiency leads to obesity and lipogenesis, possibly in part through increasing the food intake of mice fed a high-fat diet.

Surgical management of multiple ventricular septal defects: the role of the felt sandwich technique.

OBJECTIVE: Recently, the felt sandwich technique has been widely used to close muscular ventricular septal defects. We evaluated the early and midterm results of our strategy (a combination of the sandwich technique and direct closures) and assessed the role of the sandwich technique in the treatment of multiple ventricular septal defects. METHODS: Twenty-nine consecutive patients underwent an operation for multiple ventricular septal defects and associated cardiac malformations. They included 17 boys and 12 girls with a median age of 6.0 months. Thirteen patients had 4 or more ventricular septal defects (Swiss cheese septum). RESULTS: There was no surgical or follow-up mortality, and no reoperations were required. There were no cases of heart block and no significant residual shunts in the latest follow-up study. Two patients with Swiss cheese septum had postoperative congestive heart failure. Three muscular ventricular septal defects were closed with the sandwich technique in these 2 patients, whereas 1 or fewer ventricular septal defects were closed with the sandwich technique in the other 27 patients. Seven (77.8%) of 9 patients who underwent the sandwich procedure had septal dysfunction, whereas 5 (25.0%) of the other 20 patients showed septal dysfunction (P < .05). CONCLUSIONS: The outcome of the surgical repair of multiple ventricular septal defects was satisfactory. Although the sandwich technique is simple and effective, the use of numerous felt patches disturbed the movement of the interventricular septum. An effort should be made to close the muscular ventricular septal defect directly to avoid postoperative cardiac dysfunction. Large apical ventricular septal defects, especially those located just underneath the moderator band, are considered suitable for the sandwich technique.

An infected pseudoaneurysm following a modified Blalock-Taussig shunt.

A two-month-old male infant with tetralogy of Fallot underwent a right-sided modified Blalock-Taussig shunt using a 4 mm expanded polytetrafluoroethylene graft through a right thoracotomy. Five months later, the patient developed otitis media, followed by repeated relapses of pneumonia and fever of unknown origin. Multidetector-row computed tomography and angiography, performed at 12 months of age, revealed a pseudoaneurysm of the subclavian artery at the insertion of the modified Blalock-Taussig shunt. After 20 days of antibiotic therapy, the pseudoaneurysm and infected graft were successfully resected through a median sternotomy approach. This report describes the treatment strategy of this rare but potentially fatal complication after a modified Blalock-Taussig shunt operation.

Simultaneous operation of off pump coronary artery bypass and abdominal aortic aneurysm repair.

OBJECTIVES: Coronary artery disease (CAD) and abdominal aortic aneurysms (AAA) commonly coexist. However, each disease treatment complicates the management of the other. In this study, we evaluate whether a simultaneous operation of AAA repair and off pump coronary artery bypass (OPCAB) would be safe and acceptable, compared with either procedure alone. SUBJECTS AND METHODS: We retrospectively reviewed all patients who underwent simultaneous AAA repair and OPCAB (AAA/OPCAB, n=18), compared AAA repair alone (AAA, n=239) and OPCAB alone (OPCAB, n=137) from June 1999 to December 2003. There were no significant differences with regard to age or gender, but the AAA/OPCAB group had significantly larger aneurysms (60.6 vs. 53.2 mm) and significantly lower ejection fractions (EF) (54.9 vs. 60.3%). RESULTS: The patients in the AAA/OPCAB group underwent a significantly longer operative time than AAA, OPCAB (403 vs. 360, 296 minutes, respectively), there was significantly greater blood loss (726 vs. 426, 462 ml), and more transfusion required (8.13 vs. 1.69, 2.8 units). The number of bypass grafts in AAA/OPCAB group (1-5 per patients) was significantly smaller (1.78 vs. 2.93). The AAA/OPCAB patients had a significantly longer hospital stay than the AAA (38 vs. 22 days), but was not significantly longer than the OPCAB. There were no significant differences with regard to the morbidity and mortality rate among the three groups. CONCLUSION: This study suggests that the simultaneous operation of AAA and OPCAB can be done with the same morbidity and mortality as independent surgical procedures.